From the Guidelines
Elevated sex hormone binding globulin (SHBG) is primarily caused by conditions that affect liver function, hormonal balance, or metabolic health, with liver disease being a significant factor, as seen in chronic liver disease where SHBG levels rise due to increased estrogen levels and liver synthesis 1. The causes of elevated SHBG can be multifaceted, including:
- Hyperthyroidism, which increases SHBG production through enhanced liver synthesis
- Estrogen excess from conditions like pregnancy, hormone replacement therapy, or oral contraceptives
- Liver disease such as hepatitis or cirrhosis, where SHBG levels can rise due to increased estrogen levels and liver synthesis 1
- Aging, particularly in men
- HIV infection
- Certain medications including anticonvulsants and some antipsychotics
- Lifestyle factors like caloric restriction, excessive exercise, and malnutrition
- Genetic factors, as some individuals have naturally higher SHBG levels It's essential to note that elevated SHBG is clinically significant because it binds to sex hormones (particularly testosterone), reducing their bioavailability and potentially causing symptoms of hormone deficiency despite normal total hormone levels. Management typically involves addressing the underlying cause rather than treating SHBG levels directly. For medication-induced elevations, alternative treatments may be considered when appropriate, while lifestyle modifications like maintaining healthy weight and moderating exercise intensity can help normalize levels in some cases. In the context of liver disease, the relationship between SHBG and liver function is complex, with SHBG levels initially rising in chronic liver disease due to increased estrogen levels and liver synthesis, but ultimately declining in decompensated cirrhosis 1. Monitoring and management of elevated SHBG should be guided by the underlying cause, with consideration of the potential impact on sex hormone bioavailability and overall health.
From the Research
Causes of Elevated Sex Hormone Binding Globulin (SHBG)
Elevated SHBG levels can be caused by various factors, including:
- Thyroid hormones, which increase hepatic SHBG production indirectly via changes in hepatocyte nuclear factor-4alpha (HNF-4alpha) levels 2
- Certain metabolic diseases, such as obesity and metabolic syndrome, which can result in changed SHBG serum levels due to the liver's central role in metabolism 3
- Endocrine disorders, such as polycystic ovary syndrome, which can affect tissues involved in sex hormone regulation and impact SHBG levels 3
- Hyperthyroidism, which has been shown to increase SHBG levels 4
- Age, which can be a minor factor influencing SHBG levels, although to a lesser extent than thyroid status 4
Association with Other Conditions
Elevated SHBG levels have been associated with:
- Incident cardiovascular disease in men, with higher SHBG levels independently associated with a greater risk of cardiovascular disease 5
- Adverse impact on left ventricular ejection fraction (LVEF) in men with heart failure and type 2 diabetes mellitus (T2DM) 6
- Certain pathological states, such as breast and prostate cancer, osteoporosis, and metabolic syndrome, where SHBG may play a role as a mediator between various endocrine tissues 3